Significance of Mutations in the Androgen Receptor Gene in Males with Idiopathic Infertility1

• DOI: 10.1210/jcem.85.8.6713
• Publication Date: 2014-01-08T17:05:46Z
• Authors: Olaf Hiort; Paul-Martin Holte...; Thorsten Horter; Wolfgang Schulze; Britta Kremke; Monika Bals-Pratsch; Gernot H. G. Sinn...; Klaus Kruse
• Keywords: Virilization; Androgen insensitivity syndrome

Abnormal human spermatogenesis is caused by a variety of genetic and acquired conditions. Because dependent on androgens, some males may have minimal form androgen insensitivity that does not inhibit virilization but impairs fertility. This has lead us to investigate the possibility abnormalities in receptor (AR) gene large cohort suffering from infertility unknown cause. We studied 180 with variable impairment spermatogenesis. In all patients, serum levels testosterone gonadotropins were analyzed define an sensitivity index (ASI). Single-strand conformation analysis direct DNA sequencing PCR-amplified blood leukocyte used identify mutations within whole coding region AR-gene. Endocrine molecular investigations compared 53 normal proven three infertile males, AR identified. Two unrelated had same variation first exon encoding for transactivation domain (Pro390Ser), whereas, third, mutation hormone-binding was characterized (Gln798Glu). All identified carriers significantly elevated ASI. A proportion idiopathic carry relevant variations These be distinguished basis hormone levels, calculating ASI, although this lacks specificity.